PROJECT SUMMARY/ABSTRACT -OVERALL Chagas disease (ChD), caused by infection with the parasite Trypanosoma cruzi, remains one of the world's most neglected diseases with 5.7 million infected people, but only a single partially effective treatment. The lack of good biomarkers for active infection or clinical end-points poses a problem for assessing the performance of new drugs or therapeutic interventions. The Sao Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) consists of a network of collaborating scientists in the States of Minas Gerais and Sao Paulo which has been established for the purpose of developing and conducting research projects on ChD biomarker discovery and validation. In this proposal, the center will develop three interrelated studies: Project 1 will study the natural history of ChD, in order to recognize prognostic markers related to the risk of progression to cardiopathy, cardiac complications and death. To that effect, we will characterize the clinical evolution of two large cohorts (REDS and SaMi-Trop) to assess the predictable values of biomarkers measured at cohort enrollment. Project 2 will assess if genetic susceptibility modulates disease development. We will use genome wide association study (GWAS) that will combine genetic data from ~5,500 individuals recruited by two NIH-sponsored studies (REDS and SaMi-Trop) and other studies funded by Brazilian Agencies (Bambui, Heart Institute). Project 3 will determine if T cruzi vectorial transmission is reemerging in the Northen Region of Minas Gerais State (a region considered free of domiciliary vector transmission since 2006). We will conduct a large-scale screening survey to detect T. cruzi antibody in schoolchildren?s saliva, and a survey with questionnaires applied to the children?s parents about the prevalence of infestation by triatominae vectors. Two cores (Administrative/Scientific Core and Database and Epidemiology Core) will support activities of the three projects, and will seek to sustain research training capacity for young Brazilian scientists